Small-Cell Lung Cancer:Is the Black Box Finally Opening Up?

Small-cell lung cancer (SCLC) is an aggressive cancer that originates from the neuroendocrine crest [...

Pursuing More Sustainable Consumption by Analyzing Household Metabolism in European Countries and Cities

Bringing about more sustainable consumption patterns is an important challenge for society and science. In this article the concept of household metabolism is applied to analyzing consumption patterns and to identifying possibilities for the development of sustainable household consumption patterns. Household metabolism is determined in terms of total energy requirements, including both direct and indirect energy requirements, using a hybrid method. This method enables us to evaluate various determinants of the environmental load of consumption consistently at several levels—the national level, the local level, and the household level. The average annual energy requirement of households varies considerably between the Netherlands, the United Kingdom, Norway, and Sweden, as well as within these countries. The average expenditure level per household explains a large part of the observed variations. Differences between these countries are also related to the efficiency of the production sectors and to the energy supply system. The consumption categories of food, transport, and recreation show the largest contributions to the environmental load. A comparison of consumer groups with different household characteristics shows remarkable differences in the division of spending over the consumption categories. Thus, analyses of different types of households are important for providing a basis for options to induce decreases of the environmental load of household consumption. At the city level, options for change are provided by an analysis of the city infrastructure, which determines a large part of the direct energy use by households (for transport and heating). At the national level, energy efficiency in production and in electricity generation is an important trigger for decreasing household energy requirements.

Genome2D: a visualization tool for the rapid analysis of bacterial transcriptome data

Genome2D is a Windows-based software tool for visualization of bacterial transcriptome and customized datasets on linear chromosome maps constructed from annotated genome sequences. Genome2D facilitates the analysis of transcriptome data by using different color ranges to depict differences in gene-expression levels on a genome map. Such output format enables visual inspection of the transcriptome data, and will quickly reveal transcriptional units, without prior knowledge of expression level cutoff values. The compiled version of Genome2D is freely available for academic or non-profit use from

An mRNA expression-based signature for oncogene-induced replication-stress

Oncogene-induced replication stress characterizes many aggressive cancers. Several treatments are being developed that target replication stress, however, identification of tumors with high levels of replication stress remains challenging. We describe a gene expression signature of oncogene-induced replication stress. A panel of triple-negative breast cancer (TNBC) and non-transformed cell lines were engineered to overexpress CDC25A, CCNE1 or MYC, which resulted in slower replication kinetics. RNA sequencing analysis revealed a set of 52 commonly upregulated genes. In parallel, mRNA expression analysis of patient-derived tumor samples (TCGA, n=10,592) also revealed differential gene expression in tumors with amplification of oncogenes that trigger replication stress (CDC25A, CCNE1, MYC, CCND1, MYB, MOS, KRAS, ERBB2, and E2F1). Upon integration, we identified a six-gene signature of oncogene-induced replication stress (NAT10, DDX27, ZNF48, C8ORF33, MOCS3, and MPP6). Immunohistochemical analysis of NAT10 in breast cancer samples (n=330) showed strong correlation with expression of phospho-RPA (R=0.451, p=1.82x10(-20)) and γH2AX (R=0.304, p=2.95x10(-9)). Finally, we applied our oncogene-induced replication stress signature to patient samples from TCGA (n=8,862) and GEO (n=13,912) to define the levels of replication stress across 27 tumor subtypes, identifying diffuse large B cell lymphoma, ovarian cancer, TNBC and colorectal carcinoma as cancer subtypes with high levels of oncogene-induced replication stress

SETD2:an epigenetic modifier with tumor suppressor functionality

In the past decade important progress has been made in our understanding of the epigenetic regulatory machinery. It has become clear that genetic aberrations in multiple epigenetic modifier proteins are associated with various types of cancer. Moreover, targeting the epigenome has emerged as a novel tool to treat cancer patients. Recently, the first drugs have been reported that specifically target SETD2-negative tumors. In this review we discuss the studies on the associated protein, Set domain containing 2 (SETD2), a histone modifier for which mutations have only recently been associated with cancer development. Our review starts with the structural characteristics of SETD2 and extends to its corresponding function by combining studies on SETD2 function in yeast, Drosophila, Caenorhabditis elegans, mice, and humans. SETD2 is now generally known as the single human gene responsible for trimethylation of lysine 36 of Histone H3 (H3K36). H3K36me3 readers that recruit protein complexes to carry out specific processes, including transcription elongation, RNA processing, and DNA repair, determine the impact of this histone modification. Finally, we describe the prevalence of SETD2-inactivating mutations in cancer, with the highest frequency in clear cell Renal Cell Cancer, and explore how SETD2-inactivation might contribute to tumor development